A human leukemic cell line has been used to study steroid actions. Steroid resistant subclones occur spontaneously in these cells at a rate consistent with functional haploidy at the glucocorticoid receptor locus. Receptors of variant cells are more labile than those of wild-type cells. HTC cell variants have been infected with mouse mammary tumor virus (MTV) and possible interrelations between MTV and other induced functions studied. Somatic cell hybrids between GH cells and L cells show that prolactin induction by TRH and estrogen is lost, TRH induction because of loss of TRH receptor sites, estrogen induction as a result of failure to induce prolactin mRNA despite the presence of estrogen receptors. In human breast cancer, lack of progesterone receptors correlates with an improved response to chemotherapy. Steroids which are designed to be covalent affinity labels for glucocorticoid receptors are being developed. Chromosome mapping of the glucocorticoid receptor locus is being pursued. Prolactin cDNA is being cloned. A potent glucocorticoid with an unusual structure is being studied for its effect on biological systems.